DExD/H-box helicase (DDX) 5 belongs to the DExD/H-box helicase family. DDX family members play differential roles in the regulation of innate antiviral immune response. However, whether DDX5 is involved in antiviral immunity remains unclear. In this study, we found that DDX5 serves as a negative regulator of type I interferon (IFN) response. Overexpression of DDX5 inhibited IFN production induced by Spring viremia of carp virus (SVCV) and poly(I:C) and enhanced virus replication by targeting key elements of the RLR signaling pathway (MAVS, MITA, TBK1, IRF3 and IRF7). Mechanistically, DDX5 directly interacted with TBK1 to promote its autophagy-mediated degradation. Moreover, DDX5 was shown to block the interaction between TRAF3 and TBK1, hence preventing nuclear translocation of IRF3. Together, these data shed light on the roles of DDX5 in regulating IFN response.

DExD/H-box 解旋酶 （DDX） 5 属于 DExD/H-box 解旋酶家族。DDX 家族成员在先天抗病毒免疫反应的调节中起着不同的作用。然而，DDX5 是否参与抗病毒免疫仍不清楚。在这项研究中，我们发现 DDX5 是 I 型干扰素 （IFN） 反应的负调节因子。DDX5 过表达抑制鲤鱼病毒 （SVCV） 和 poly （I：C） 春季病毒血症诱导的 IFN 产生，并通过靶向 RLR 信号通路的关键元件 （MAVS、MITA、TBK1、IRF3 和 IRF7） 增强病毒复制。从机制上讲，DDX5 直接与 TBK1 相互作用，促进其自噬介导的降解。此外，DDX5 被证明可以阻断 TRAF3 和 TBK1 之间的相互作用，从而阻止 IRF3 的核转位。总之，这些数据阐明了 DDX5 在调节 IFN 反应中的作用。